Pipelines

Gene Therapy

HighField Pipeline

HighField Pipeline Products

K16: Immune Modulator

Update: In Phase I, K16 has shown a 69% disease control rate as a single agent therapy for heavily pretreated patients with recurring glioma. An open label, multicenter phase 2 trial will initiate soon to evaluate the safety and efficacy of K16 in combination with standard of care (SOC) for patients with locally advanced or metastatic pancreatic and non-small cell lung cancers, and glioblastoma.

K16 combines a lipid bilayer structure and all-trans retinoic acid (ATRA). In high concentrations, ATRA can induce immature immune cells (MDSCs) to become mature, active immune cells (dendritic cells).

MDSCs have an immune suppressive activity, so converting them to mature active immune cells generates an anticancer effect. Moreover, cancer patients tend to accumulate MDSCs beyond what is found in healthy people and also accumulate them in the tumors themselves. This is a particularly insidious suppression of the immune systems of cancer patients that when reversed can have a profound effect on tumors.

As ATRA is a metabolite of vitamin A, this lipid system has demonstrated a high degree of safety in human trials. In the initial human trial data, this lipid system has also shown a strong signal of single-agent efficacy in cancer, particularly in brain tumors .

Beyond this, given its strong safety profile and unique mechanism against tumors, K16 is a prime candidate for combination with other cancer therapeutics.

K1: ADCplex™ Lipid-based Antibody Drug Complex

This drug-encapsulated immunoliposome represents a new generation of targeted cancer therapy

Our ADCplex platform offers greater payload capacity and flexibility than other targeted therapeutics such as antibody-drug conjugates (ADCs). This allows for greater safety while also improving the therapeutic effect, resulting in a larger therapeutic window.

Kl is the most advanced ADCplex under development in our pipeline. It contains the antibody lipid TL01, which is directed to HER2. The encapsulated drug payload is doxorubicin. In animal models, K1 has higher anti-tumor activities than the leading drugs, such as T-DM1 and DS-8201a. Importantly, K1 had no associated chemo-resistance effect that is found in these other drugs.

Update: In Phase I clinical studies, K1 has also been shown to be safe at doxorubicin dose level of 30mg/m2. The first patient treated has achieved PFS of over 6 months

HF50: TCEplex™ T cell Engager Complex

HF50 is currently in Phase 1 clinical trial. The open label, dose escalation trial in China will assess safety, tolerability, pharmacokinetic characteristics, immunogenicity, and preliminary efficacy. Details of the study design and contacts are on ClinicalTrials.gov (NCT06822998).

Directing T cells towards cancer cells and enhancing anticancer activity with an immune modulator

HF50 is a lipid bilayer system with two different antibodies attached. The first is directed to immune T cells, while the second antibody is directed to HER2 expressing tumors. This system is called T cell Engager Complexes, or TCEplex. HF50 also carries a payload of Resiquimod, a small molecule compound that modulates T cell response toward cancer cells.

By optimizing these components to each other and to HER2 expressing tumors, relevant animal model data show this to be effective against HER+ tumors. Moreover, this is the first systemic use of Resiquimod, and data show that stimulating the immune T cells in this manner greatly enhances the anti-tumor activity.

This lipid system can be compared to a bispecific antibody but exceeds it in many aspects. Bispecifics have very limited antibody conjugation schemes. An optimal ratio of the components cannot be achieved. This limits the therapeutic window and their efficacies in solid tumors.

HF50 as an enhanced CAR T is a more apt comparison. The goal of CAR T is to produce T cells expressing anti-tumor antibodies on their outer membrane. HF50 achieves this goal without the complex and expensive processing inherent in CAR T-cell therapies. Moreover, the immunomodulatory payload also plays an important role in enhancing T cell activity.

HFG1: tLNPplex™ LND-mRNA Complex

HFG1 is presently in IND enabling studies. The preclinical studies showed that HFG1 required far fewer injections than existing GLP-1 products while providing steady-state agonist activity.

Gene therapy for very long term expression of GLP-1R agonist

HFG1 is an LNP-mRNA complex that provides expression of a GLP-1R agonist for weight loss and treating diabetes. HFG1 is presently in IND enabling studies for a U.S. IND filing.

The components of HFG1’s LNP complex were selected to provide prolonged expression of the GLP-1R agonist without observable immune response. HFG1 requires fewer injections than existing GLP-1 products while providing steady-state agonist activity.

Diabetic monkeys treated with HFG1 show weight loss and significant A1C reduction over an extended period. After an initial activity peak at dosing, a steady state of GLP-1R activity and A1C control were observed for at least 60 days. This translates into therapeutic activity of about 4-5 months in humans for a single injection. No behavior changes or toxicities were observed other than an initial loss of appetite at the time of injection.